Department of Health Sciences, University of Molise, Campobasso, Italy.
Mol Neurobiol. 2011 Oct;44(2):192-201. doi: 10.1007/s12035-011-8181-5. Epub 2011 Apr 19.
In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation ofNrf2 target genes, and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death. In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial role in the pathogenesis of neurodegenerative disorders. Recent and unpublished data from our group revealed that low concentrations of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction. These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against cognitive decline.
近年来，越来越多的实验和流行病学研究支持了一种观点，即某些存在于常用香料和草药中的酚类物质具有有益作用，可以预防各种与年龄相关的病理状况，包括癌症和神经退行性疾病。尽管多酚促进这些作用的确切机制仍有待阐明，但有几项报告显示，它们能够刺激靶细胞中的一般异生素反应，激活多种防御基因。我们和其他实验室的数据先前已经证明，咖喱中的黄色色素姜黄素通过激活 NF-E2 相关因子 2 (Nrf2)/抗氧化反应元件 (ARE) 途径的异二聚体，强烈诱导不同脑细胞中的血红素加氧酶-1 (HO-1) 表达和活性。许多研究清楚地表明，星形胶质细胞和神经元中 Nrf2 靶基因的激活，特别是 HO-1 的激活，对炎症、氧化损伤和细胞死亡具有强烈的保护作用。在中枢神经系统中，已经报道 HO 系统非常活跃，其调节似乎在神经退行性疾病的发病机制中起着关键作用。我们小组最近和未发表的数据显示，表没食子儿茶素-3-没食子酸酯（EGCG），即绿茶中主要的儿茶素，通过 ARE/Nrf2 途径诱导海马神经元中的 HO-1，通过这种诱导，它能够保护神经元免受不同的氧化损伤模型的损害。此外，我们已经证明，其他酚类物质，如咖啡酸苯乙酯和阿魏酸乙酯，也能够通过诱导 HO-1 来保护神经元。这些研究确定了一类新的化合物，它们可以作为预防认知能力下降的治疗药物。
